DESCRIPTION (provided by principal investigator): Owing to a legacy of industrial pollution throughout the 20th Century, families and children in the in the United States are exposed to mixtures of environmental contaminants;one of the most significant contaminants is polychlorinated biphenyls (PCBS). PCBs demonstrate multiple forms of neurotoxicity, most notably with regard to dopamine (Mariussen &Fonnum, 2006) and white matter development (Sharlin et al. 2006;Preliminary Studies). This investigative team has shown a link between exposure to PCBs and impulsive behavior, or more specifically, impaired response inhibition (Stewart et al. 2003, 2005, 2006). This highly circumscribed behavioral deficit, characterized by an impaired ability to withhold responses, is associated with a rich brain imaging literature that implicates a number of frontal and fronto-striatal structures in its regulation. The importance of the link between response inhibition and brain function in this cohort is underscored by the finding of significant reductions in white matter throughout the cerebral cortex, especially the frontal cortex, in our PCB-exposed children. We intend to investigate whether PCB exposure and impaired response inhibition is related to impaired activation of the prefrontal cortex (inferior) and if those activational changes are related to reductions in white matter integrity in frontostriatal tracts. The proposed study will capitalize on an 18 year longitudinal study of child development, in combination with state-of-the-art neuroimaging approaches at the Rochester Center for Brain Imaging (RCBI). The Specific Aims are: AIM #1) To test the hypothesis that altered activation of the prefrontal cortex (PFC) underlies the PCB-related deficits in impulse control (response inhibition). AIM #2) To test the hypothesis that frontostriatal connectivity is reduced in PCB exposed children. PUBLIC HEALTH RELEVANCE: There is reasonable evidence from research studies that indicate that prenatal exposure to PCBs produces impairments in cognitive and behavioral development in children. The Oswego Project represents one of the few major, longitudinal studies in the United States designed to assess the effects of exposure to low levels of PCBs on child development. The stable nature of the cohort, the 16 years of experience the principal investigators have with these cohorts, the well-established testing protocols, and the extensive database of exposure, outcome and potentially confounding/mediating variables permit rigorous assessment of the impact of prenatal PCB exposure in the teen years.